6-15307653-C-T

Variant names:

• chr6-15307653-C-T
• rs16876210
• NM_004973.4:c.45+61069C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004973.4(JARID2):​c.45+61069C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,180 control chromosomes in the GnomAD database, including 1,637 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1637 hom., cov: 32)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289
• Publications: 0 publications found

Genes affected

JARID2 (HGNC:6196): (jumonji and AT-rich interaction domain containing 2) This gene encodes a Jumonji- and AT-rich interaction domain (ARID)-domain-containing protein. The encoded protein is a DNA-binding protein that functions as a transcriptional repressor. This protein interacts with the Polycomb repressive complex 2 (PRC2) which plays an essential role in regulating gene expression during embryonic development. This protein facilitates the recruitment of the PRC2 complex to target genes. Alternate splicing results in multiple transcript variants. Mutations in this gene are associated with chronic myeloid malignancies. [provided by RefSeq, May 2012]

JARID2 Gene-Disease associations (from GenCC):

• developmental delay with variable intellectual disability and dysmorphic facies

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004973.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JARID2	NM_004973.4	MANE Select	c.45+61069C>T		intron	N/A	NP_004964.2
	JARID2	NM_001267040.1		c.-472+58689C>T		intron	N/A	NP_001253969.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JARID2	ENST00000341776.7	TSL:1 MANE Select	c.45+61069C>T		intron	N/A	ENSP00000341280.2
	JARID2	ENST00000853926.1		c.45+61069C>T		intron	N/A	ENSP00000523985.1
	JARID2	ENST00000853927.1		c.45+61069C>T		intron	N/A	ENSP00000523986.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18860 AN: 152062 Hom.: 1627 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.0701

Gnomad ASJ AF: 0.0600

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.0758

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0720

Gnomad OTH AF: 0.112

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.124 AC: 18907 AN: 152180 Hom.: 1637 Cov.: 32 AF XY: 0.126 AC XY: 9343 AN XY: 74398

African (AFR) AF: 0.239 AC: 9902 AN: 41514

American (AMR) AF: 0.0699 AC: 1069 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0600 AC: 208 AN: 3468

East Asian (EAS) AF: 0.153 AC: 792 AN: 5180

South Asian (SAS) AF: 0.183 AC: 881 AN: 4826

European-Finnish (FIN) AF: 0.0758 AC: 801 AN: 10574

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0720 AC: 4898 AN: 68004

Other (OTH) AF: 0.114 AC: 242 AN: 2116

Alfa AF: 0.0897 Hom.: 478

Bravo AF: 0.126

Asia WGS AF: 0.174 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.0
DANN	Benign	0.54
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs16876210; hg19: chr6-15307884;